Dry eye syndrome is a very common disease reported to have a prevalence of 5.5-15% depending on study population, age and diagnosis standard, which are used in various epidemiological studies in the world. This disease is characterized by ocular pain, an irregular corneal surface, blurred and fluctuating vision, and increased risk of corneal ulcer. The change in corneal permeability caused by chronic dry eyes and keratitis sicca resulting from unstable tear film has been known to cause inflammations, which has been demonstrated by increased inflammation-mediated chemokine and cytokine in tears, increased immune activity and expression of adhesion molecules (HLA-DR and inter-cellular adhesion molecule 1 [ICAM-1]) by conjunctival epithelial cells, and increased T lymphocytes in the conjunctiva. Corneal ulcer resulting from keratoconjunctivitis sicca (KCS) may lead to poor vision, vision loss and, even blindness. It has been reported that the level and activity of matrix metalloproteinase-9 (MMP-9) greatly increase not only in the tears of patients with dry eye syndrome, but also in the corneal epithelium and tears of experimental dry eye (EDE) mice. Dry eye syndrome is a disorder of the tear film due to tear deficiency or changes in tear components, which is accompanied by various symptoms of ocular discomfort. Recently, the definition of dry eye syndrome has expanded, because as new types of dry eye syndromes with a neurogenic component (such as dry eyes that occur after LASIK procedures), ocular surface diseases due to an altered tear film composition, and the like have occurred (American Journal of Ophthalmology, 140. 507, 2005).
Dry eye syndrome is found in more than 50% of total patients visiting ophthalmic clinics, and the elderly, particularly 70 to 80% of post-menopausal women, suffer from ocular discomfort due to dry eye syndrome. In the past, it was considered that the pathological cause of dry eye syndrome was the aqueous layer deficiency resulting from decreased tear production by the lacrimal glands. However, in recent years, it has been found that the primary causes of dry eye syndrome are inflammatory responses to external stimuli, or endogenous inflammatory responses, which cause problems associated with chronic ocular surface damage arising from disorders of corneal epithelial cells, and decreased interactions between corneal epithelial cells and corneal keratocytes. Dry eye syndrome may be developed by various causes such as aging, hormonal changes, environmental factors (wind, heat, dust, cigarette smoke, hair dryers, etc.), a chronic low blink rate (VDT syndrome), contact lens wear, LASIK vision correction surgery, medications, and autoimmune diseases (lupus, rheumatoid arthritis and Sjogren's syndrome) (American Journal of Ophthalmology, 137, 337-342, 2004).
Meanwhile, NASAID, a non-specific COX enzyme inhibitor that is used to alleviate inflammation, has the effect of reducing prostaglandin levels in a non-specific manner. This drug is known to alleviate inflammation and pain, but is also known to produce inflammatory products such as leukotrienes, lipoxins, hydroperoxyeicosatetraenoic acids and the like. In the ophthalmic field, non-specific COX enzyme inhibitors have been developed and used as eye drops, but serious side effects such as corneal perforation, which are caused by the activation of the above inflammatory products, have been reported.
Accordingly, the present inventors have made extensive efforts to develop a pharmaceutical composition for treating or treating ocular diseases, including dry eye syndrome, which cause ocular pain. As a result, the present inventors have found that the expression level of prostaglandin E2 (PGE2) is higher in the tears of patients having an ocular pain symptom than in the tears of normal peoples and that when a PGE2 synthesis inhibitor is dropped into the eyes of animal models, it exhibits the effect of treating ocular pain, thereby completing the present invention.